Biodegradable Polydioxanone Microspheres for Transcatheter Arterial Embolization: Proof of Principle

PurposeTo evaluate feasibility, embolization success, biodegradability, reperfusion, and biocompatibility of biodegradable microspheres (MS) made from polydioxanone (PDO) for transcatheter arterial embolization.Materials and MethodsUnilateral selective renal embolization of a segmental artery was performed in 16 New Zealand White rabbits with PDO-MS (100–150 μm and 90–315 μm). Animals were randomly assigned to different observation periods and underwent control digital subtraction angiography (DSA) and MR imaging immediately (n = 3), 1 week (n = 2), 4 weeks (n = 2), 8 weeks (n = 2), 12 weeks (n = 5), and 16 weeks (n = 2) after embolization. Kidneys were harvested for macroscopic and histologic analysis of embolization success, biodegradability, and biocompatibility.ResultsEmbolization was technically successful in 15 of 16 animals. One animal died of anesthesia-related circulatory failure. The 100–150 μm MS were injected easily through 3-F catheters; the 90–315 μm MS tended to clog with intermittent catheter obstruction. DSA and MR imaging showed successful target embolization in 13 of 15 animals. In 2 animals, the entire kidney was affected owing to catheter clogging, including a reflux of MS while flushing. Control DSA and MR imaging showed increasing vascular reperfusion with time. Macroscopic and histologic analysis revealed necrosis/infarction in areas in which embolization was achieved. MS were extensively degraded after 16 weeks, and overall inflammatory reaction was mild.ConclusionsBiodegradable PDO-MS induced effective embolization of target vessels while demonstrating good biocompatibility. MS increasingly dissolved at 16 weeks, partial reperfusion started at week 1, and complete reperfusion started at week 8, thus offering possible advantages as a temporary embolic agent.     

可吸收明胶海绵棒在椎弓根内止血的应用

[目的]观察评价可吸收明胶海绵棒在椎弓根置钉过程中的止血效果。[方法]2017年10月~2018年6月,48例胸腰椎骨折即将行后路手术的患者纳入本研究,采用随机数字表法分为明胶海绵组和骨蜡组。明胶海绵组共23例,置钉过程中应用明胶海绵棒填塞至椎弓根孔道止血;骨蜡组共25例,在透视定位时应用骨蜡封闭椎弓根孔道。记录置钉情况;记录术中出血量、自体血回输量、置钉过程中的出血量、输血量;检测术前和术后5 d RBC、HB和HCT。[结果]两组在置钉总数、伤椎置钉数、伤椎位置各椎置钉数量的差异均无统计学意义(P>0.05)。术后两组各出现1例小腿肌间静脉血栓,抗凝治疗后于复查时消失。术后两组均无明胶海绵或骨蜡导致的不良反应。两组在术中出血量、术中自体血回收量、输血量的差异无统计学意义(P>0.05),但明胶海绵组上述指标均小于骨蜡组。每钉置入过程中明胶海绵组的出血量显著少于骨蜡组,差异有统计学意义(P<0.05)。两组术后5 d的RBC、HB和HCT均较术前显著减少,两时间点间差异均有统计学意义(P<0.05)。术前两组在RBC、HB和HCT的差异均无统计学意义(P>0.05),术后5 d两组在RBC、HB和HCT的差异亦均无统计学意义(P>0.05)。[结论]应用明胶海绵棒填塞椎弓根孔道止血可显著减少安置椎弓根螺钉过程中的出血,是一种简单、安全、有效的脊柱外科术中止血方法。     

胶原蛋白海绵在皮肤扩张术中的应用

目的：观察胶原蛋白海绵在皮肤扩张术中的临床应用效果。方法：选择40例（个）皮肤扩张器埋置和50例（个）皮肤扩张器取出及15例自身对照的病例组,应用胶原蛋白海绵术中贴敷于渗血创面,术后观察其吸收、止血效果。结果：术中渗血于2～10min内停止,病例组中无血肿发生,术后引流量明显减少,伤口愈合时间缩短。结论：在皮肤扩张术中胶原蛋白海绵是一种良好的生物止血材料。     

Epithelial tissue formation in matrix culture and in histophysiologic gradient culture

Summary Formation of epithelial tissues in culture so that they become facsimiles in their structure of such tissues in nature requires procedures that comply with several spatial imperatives: a) three-dimensional growth; b) histophysiologic conditions that provide, concurrently, gradients of maturation and of diffusion of metabolites; and c) growth as layers of cells without free edges. Many steps have been required in the evolution of these methods. Two systems are described here in sufficient detail to serve as a manual. Three-dimensional growth of masses of epithelial tissue is accomplished in matrix culture using Gelfoam sponge and collagen-coated cellulose sponge. Radial gradient culture, a recent development, provides conditions that comply with the requirements of histophysiologic gradients and of epithelial tissue growth in layers without interruption in their continuity.     

Regional gene therapy for full-thickness articular cartilage lesions using naked DNA with a collagen matrix.

A novel gene therapy approach for treating damaged cartilage is proposed that involves placing endotoxin-free cDNA containing the gene for bone morphogenetic protein-2 (BMP-2) in type I collagen sponges and then transferring the naked plasmid DNA construct to the injury site. A full-thickness cartilaginous defect in rabbits implanted with plasmid containing a marker gene (beta-galactosidase) showed expressed protein as detected by immunostaining. At 1 week postimplantation, mesenchymal cells subjacent to the defect had incorporated the implanted naked plasmid DNA and, once transfected, served as local bioreactors, transiently producing the gene product. Plasmids containing the gene for BMP-2 implanted in collagen sponges in cartilage lesions stimulated hyalinelike articular cartilage repair at 12 weeks postimplantation, nearly equivalent in quality to that induced by collagen sponges with recombinant BMP-2 protein. Our approach circumvents the risks of inflammation and immunogenic response associated with the use of viral vectors. Naked plasmid DNA as a vehicle for transferring therapeutic genes has been shown to be effective in a therapeutic model within rabbit articular cartilage and appears to be safe and cost effective.     

Medullary sponge kidneys and unilateral Wilms tumour in a child with Beckwith-Wiedemann syndrome

The occurrence of a Wilms tumour in a 4-year-old girl with bilateral medullary sponge kidney, Beckwith-Wiedemann syndrome and congenital hemihypertrophy demonstrates the close relationship between these disorders. Another six cases from the literature with congenital hemihypertrophy and with medullary sponge kidney are discussed, two of them also developed intra-abdominal neoplasm.     

Transcatheter arterial embolization of abnormal neovessels in a swine model of knee arthritis

BackgroundIn recent years, transcatheter arterial embolization (TAE) using imipenem/cilastatin (IPM/CS) has attracted attention as a treatment for relieving osteoarthritis (OA) pain. However, IPM/CS is not approved by Japanese medical insurance for use as an embolic material. Therefore, it is necessary to develop new embolic materials for TAE to relieve OA pain. The purpose of this study was to develop a swine model of knee arthritis and embolize abnormal neovessels (ANs) using two different embolic materials. We compared the embolic effects and tissue damage in knees.MethodsKnee arthritis was induced by intra-articular injection of papain into 12 knees in six female swine. The swine were divided into two groups of three swine each (six knees per group) for embolization of ANs in the knees with either IPM/CS or soluble gelatin sponge particles (SGSs). Three days after embolization, we compared the embolic effects using angiography and the tissue damage histopathologically.ResultsANs were observed in all 12 knees at 42 days after papain injection. The ANs disappeared and the patent arteries were recanalized 3 days after TAE in all 12 knees. Histopathological evaluation revealed synovitis changes, such as synovial thickening and inflammatory cell infiltration, in all 12 knees. There was no evidence of skin or muscle necrosis in either group. The appearance of ANs, recanalization of the parent arteries, and histopathological outcomes were not significantly different between the two groups.ConclusionSGSs were as safe as IPM/CS for TAE of ANs in this swine model of knee arthritis.     

Autologous rib perichondrial grafts in experimentally induced osteochondral lesions in the sheep-knee joint: Morphological results

Summary The purpose of the present study was to examine the fate of autologous perichondrial grafts after transplantation into cartilage lesions in weight-bearing joints. Osteochondral lesions were made in the articular surface of knee joints in 36 sheep. The defects were filled with autologous rib perichondrial grafts which were secured by either collagen sponges (12 animals) or fibrin glue (12 animals). Defects without perichondrial grafts served as controls (12 animals). Following 1 week of immobilization of the operated leg, the plaster was removed and the animals were allowed to move freely. Animals were sacrificed after 4, 8, 12 and 16 weeks. The grafts were removed and investigated histologically. In contrast to weight-bearing areas and control defects, hyaline-like cartilage formation was seen in non-weightbearing areas after 4 weeks. This newly formed cartilage revealed strong metachromasia following staining with acidic toluidine blue and reacted positively with periodic acid-Schiff, indicating de novo synthesis of proteoglycans and glycoproteins. Scanning electron microscopy and examinations with polarized light confirmed a hyaline cartilage-like architecture for the surface area as well as for the fibre orientation of the whole graft. Enzyme histochemistry for alkaline and acid phosphatase activity showed positive reactivity only at the base of the transplants.     

FD-1冷冻干燥机的研制及生物材料的冷冻干燥

观察自制冷冻干燥机冷冻干燥生物材料的效果。采用 R5 0 2压缩机和制冷剂制成 FD- 1冷冻干燥机。本实验冷冻干燥了胶原海绵、菌种及去纤酶。在冻干箱负载或空载情况下蒸发冷凝器温度均可达到 - 4 5℃ ,小冰箱可达到 - 30℃ ,冻干的胶原海绵具有许多孔洞的结构 ,冻干的菌种和去纤酶性能保持良好。 FD- 1冷冻干燥机适用于生物样品中小批量的冷冻干燥     

Phenotypic characterization and analysis of allogeneic T cell responses in ZAP-70 dominant negative transgenic mice

Antigen stimulation of T cells results in a series of biochemical events including the interaction of both SH2 domains of ZAP-70 with phosphorylated ITAMS on the T cell receptor. In order to study the physiological relevance of decreasing native ZAP-70–SH2 interaction in vivo, we generated transgenic mice expressing a T cell-specific, dominant negative form of ZAP-70 consisting of only the tandem SH2 domains (ZAP-NC). Phenotypically, these animals had a comparable distribution of lymphocyte subsets in the thymus and spleen compared with the wild-type (WT) controls. However, examination of peripheral blood revealed a slow but progressive decrease in the number of lymphocytes, particularly CD4⁺ cells, with age (17% reduction by 3 months, 58% reduction by 6 months). Allogeneic responses were then evaluated in vitro as well as in vivo using a subcutaneous sponge matrix implant. Although spleen cells cultured for 4 days in vitro with alloantigen developed normal functional responses, allogeneic responses generated in vivo within a subcutaneous sponge matrix were impaired. This was characterized by a depression in cytotoxic T lymphocyte (CTL) activity, a 82% reduction in the frequency of helper T cells, and a 78% reduction in the capacity of sponge-infiltrating lymphocytes to produce IL-2 in response to secondary antigen stimulation. These results indicate that although overt lymphocyte development and in vitro function were unremarkable, expression of a truncated ZAP-70 affected the in vivo survival of peripheral lymphocytes and altered the in vivo generation of functional activity to alloantigen.